PROJECT SUMMARY/ABSTRACT Pediatric overweight and obesity continue to be major public health issues. Loss of control (LOC) eating is an obesity-related phenotype that affects approximately 30% of children and adolescents with overweight/obesity and may impede successful weight control. Pediatric overweight/obesity and LOC eating frequently emerge during childhood and adolescence, and tend to follow a chronic and unremitting course if untreated. Both conditions are associated with relative deficiencies in executive functioning (EF), including working memory, planning, inhibitory control, and decision-making. These decrements may impair one?s ability to appropriately regulate weight and eating behavior. A limitation of prior research is that it has been primarily cross-sectional in nature, which inhibits understanding of the timing and direction of influence involved in the associations among EF, weight change, and eating pathology. Moreover, little is known about the domain specificity of relative EF deficits in youth with overweight/obesity and LOC eating, nor about their underlying neural substrates. An improved understanding of the nature and prospective outcomes of EF impairments in youth with overweight/obesity and LOC eating could inform intervention development by indicating whether treatments should focus on improving general and/or food-specific EF, as well as which neural pathways should be targeted to achieve the most robust and sustained effects on eating and weight. The proposed R01 study will examine prospective associations between EF performance and related neural substrates, and child weight change and LOC eating. Community-based children representing a spectrum of risk, including non- overweight/obese (n=60), overweight/obese (n=60), and overweight/obese with comorbid LOC eating (n=60), will provide repeated assessments of height/weight, LOC eating pathology, and general and food-specific EF every 6-12 months over 2 years of follow-up. A subset of participants from each risk category will complete a baseline and 18-month fMRI protocol assessing neural substrates of general and food-specific working memory. Specific aims are to investigate prospective associations between both general and food-specific EF, and their neural substrates, and trajectories of weight change and LOC eating (including remittance and persistence) over 2 years. These data will clarify timing and trajectory of weight change and LOC eating in relation to EF performance and its associated neural activation patterns. This study, which is the first to prospectively examine associations among general and food-specific EF, weight trajectories, and LOC eating, has clear potential to advance scientific and clinical understanding of mechanisms that promote the onset and maintenance of maladaptive eating in youth and inform interventions to alleviate their cumulative personal and societal burden. Furthermore, this application builds on the principal investigator?s programmatic line of research on neurocognitive factors involved in eating- and weight-related problems, and provides a clear pathway to future clinically and scientifically impactful studies.